Recent study aimed to fabricate pH responsive, intelligent, Pluronic F127 based polymeric system for controlled delivery of Famciclovir. Nine formulations were developed through free radical polymerization. Polymeric system exhibited pH dependent swelling by showing higher degree of swelling in simulated intestinal fluid of pH 7.4 while negligible swelling in simulated gastric fluid of pH 1.2. Drug loading increased with increase in percent water content. Famciclovir loading percent was found in range of 60.892% to 73.741%. In FTIR spectra, characteristic peaks were achieved confirming the successful grafting of drug in polymeric system. PXRD results demonstrated the conversion of crystalline nature of Famciclovir into an amorphous one in the loaded hydrogel. SEM confirmed the porous nature of hydrogel. Famciclovir loaded hydrogel showed superior thermal behavior as compared to the drug alone. In vitro Famciclovir release studies unveiled small quantity of drug release in simulated gastric fluid (25.55-34.89%) while maximal release in simulated intestinal fluid (90.12-99.13%) for 36 h was documented thereby confirming pH regulated release. Application of DD solver revealed that PLMA hydrogels followed zero order while First order was being followed by Famciclovir marketed tablet. No toxicity signs were observed in rabbits establishing the biosafety of system. Hence, the results suggest that Pluronic based polymeric system can act as promising carrier for controlled, site specific delivery of Famciclovir in intestine for prolonged period thereby reducing its dosing frequency and minimizing gastric side effects for treating Herpes and Varicella zoster infections.